Thyroid nodules are present in a large fraction of healthy individuals. Between 4% and 7% of the United States adult population has palpable thyroid nodules, and up to 50% of American women older than age 50 have nodules that can be depicted on ultrasound. The vast majority (>95%) of thyroid nodules are benign. However, cancer risk increases with male gender, nodule size, extremes of age (< 30 and > 60 years), underlying autoimmune disease, nodule growth, personal or family history of thyroid cancer, and radiation exposure. Ultrasound imaging and Fine Needle Aspiration Biopsy (FNAB) remain the mainstays of thyroid nodule evaluation. Unfortunately, 25% of patients who ultimately undergo FNAB of a thyroid nodule have indeterminate cytology. Many of these patients will require at least partial thyroidectomy purely for the purpose of obtaining a definitive diagnosis. Given that only 30% of these will ultimately prove to be malignant on surgical pathology, the majority of these lobectomies could potentially be avoided if better non-invasive methods existed to evaluate indeterminate nodules. Electrical Impedance Scanning (EIS) has been previously investigated for non-invasive evaluation of thyroid nodules. The overall diagnostic accuracy of EIS was encouraging but not sufficient for routine clinical use. We have developed a modified approach termed here Resonance Electrical Impedance Spectroscopy (REIS) that should have substantially higher sensitivity and specificity for this very purpose. When using REIS technology to examine the breast, we obtained initial results that are significantly better in all respects than those obtained with traditional EIS. We believe that REIS technology will similarly improve the assessment of thyroid nodules. REIS hold promise as a reproducible modality for the risk stratification of the many patients with indeterminate thyroid nodules. It is a new non- invasive modality that may help reduce the number of diagnostic lobectomies and would be welcomed by patients with non-diagnostic FNA results. The purpose of this application is to design, assemble, and test in a preliminary clinical study a unique REIS based device for the assessment of thyroid nodules. PUBLIC HEALTH RELEVANCE: We propose to design, assemble, and test in technical and preliminary human studies a non-invasive, easy to use device for measuring Resonance Electrical Impedance Spectroscopy (REIS) of FNA indeterminate thyroid nodules. We will assess the ability of this technology to accurately characterize these indeterminate nodules as benign or malignant prior to a diagnostic surgery.